As is known, microfluidic devices are being used in an increasing number of applications. However, further expansion of the uses for such microfluidic devices has been limited due to the difficulty and expense of utilization and fabrication. It can be appreciated that an efficient and simple method for producing pressure-based flow within such microfluidic devices is mandatory for making microfluidic devices a ubiquitous commodity.
Several non-traditional pumping methods have been developed for pumping fluid through a channel of a microfluidic device, including some which have displayed promising results. However, the one drawback to almost all pumping methods is the requirement for expensive or complicated external equipment, be it the actual pumping mechanism (e.g., syringe pumps), or the energy to drive the pumping mechanism (e.g., power amplifiers). The ideal device for pumping fluid through a channel of a microfluidic device would be semi-autonomous and would be incorporated totally at the microscale.
The most popular method of moving a fluid through a channel of a microfluidic device is known as electrokinetic flow. Electrokinetic flow is accomplished by conducting electricity through the channel of the microfluidic device in which pumping is desired. While functional in certain applications, electrokinetic flow is not a viable option for moving biological samples through a channel of a microfluidic device. The reason is twofold: first, the electricity in the channels alters the biological molecules, rendering the molecules either dead or useless; and second, the biological molecules tend to coat the channels of the microfluidic device rendering the pumping method useless. Heretofore, the only reliable way to perform biological functions within a microfluidic device is by using pressure-driven flow. Therefore, it is highly desirable to provide a more elegant and efficient method of pumping fluid through a channel of a microfluidic device.
In addition, as biological experiments become more complex, an unavoidable fact necessitated by the now apparent complexity of genome-decoded organisms, is that more complex tools will be required. Presently, in order to simultaneously conduct multiple biological experiments, plates having a large number (e.g. either 96 or 384) of wells are often used. The wells in these plates are nothing more than holes that hold liquid. While functional for their intended purpose, it can be appreciated that these multi-well plates may be used in conjunction with or may even be replaced by microfluidic devices.
To take advantage of existing hardware, “sipper” chips have been developed. Sipper chips are microfluidic devices that are held above a traditional 96 or 384 well plate and sip sample fluid from each well through a capillary tube. While compatible with existing hardware, sipper chips add to the overall complexity, and hence, to the cost of production of the microfluidic devices. Therefore, it would be highly desirable to provide a simple, less expensive alternative to devices and methods heretofore available for pumping fluid through a channel of a microfluidic device.
Therefore, it is a primary object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device, which is simple and inexpensive.
It is a further object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device, which is semi-autonomous and requires only minimal additional hardware.
It is a still further object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device which is compatible with preexisting robotic high throughput equipment.
In accordance with the present invention, a method is provided for pumping a sample fluid through a channel of a microfluidic device. The channel has an input and an output. The method comprises the steps of filling the channel with a channel fluid and depositing a reservoir drop of a reservoir fluid over the output of the channel. The reservoir drop has sufficient dimension to overlap the output of the channel and to exert an output pressure on the channel fluid at the output of the channel. A first pumping drop of the sample fluid is deposited at the input of the channel to exert an input pressure on the channel fluid at the input of the channel that is greater than the output pressure such that the first pumping drop flows into the channel through the input.
A second pumping drop of the sample fluid may be deposited at the input of the channel after the first pumping drop flows into the channel. The input of the channel has a predetermined radius and the first pumping drop has a radius generally equal to the predetermined radius of the input of the channel. The first pumping drop has a user selected volume and projects a height above the microfluidic device when deposited at the input of the channel. The radius of the first pumping drop is calculated according to the expression:
  R  =            [                                    3            ⁢            V                    π                +                  h          3                    ]        ⁢          1              3        ⁢                                  ⁢                  h          2                    wherein: R is the radius of the first pumping drop; V is the user selected volume of the first pumping drop; and h is the height of the first pumping drop above the microfluidic device.
The method of the present invention may include sequentially depositing a plurality of pumping drops at the input of the channel after the first pumping drop flows into the channel. Each of the plurality of pumping drops is deposited at the input of the channel in response to a previously deposited pumping drop flowing into the channel. The volume of the first pumping drop and the plurality of pumping drops are generally equal. It is contemplated that the reservoir fluid and the channel fluid be the same as the sample fluid and that the output pressure exerted by the reservoir drop be generally equal to zero.
In accordance with a still further aspect of the present invention, a method of pumping fluid includes a microfluidic device having a channel therethrough. The channel has an input port of a predetermined radius and an output of a predetermined radius. The channel is filled with fluid and a pressure gradient is generated between the fluid at the input port and the fluid at the output port such that the fluid flows through the channel towards the output port.
The pressure gradient is generated by depositing a reservoir drop of fluid over the output port of the channel of sufficient dimension to overlap the output port and by sequentially depositing pumping drops of fluid at the input port of the channel. Each of the pumping drops has a radius generally equal to the predetermined radius of the input port of the channel. The reservoir drop has a radius greater than the radii of the pumping drops and greater than the predetermined radius of the output port of the channel. The channel through the microfluidic device has a resistance and each of the pumping drops has a radius and a surface free energy. The reservoir drop has a height and a density such that fluid flows through the channel at a rate according to the expression:
            ⅆ      V              ⅆ      t        =            1      Z        ⁢          (                        ρ          ⁢                                          ⁢          gh                -                              2            ⁢                                                  ⁢            γ                    R                    )      wherein: dV/dt is the rate of fluid flowing through the channel; Z is the resistance of the channel; ρ is the density of the reservoir drop; g is gravity; h is the height of the reservoir drop; γ is the surface free energy of the pumping drops; and R is the radius of the pumping drops.
In accordance with a still further aspect of the present invention, a method of pumping fluid through a channel of a microfluidic device is provided. The channel has an input port of a predetermined radius and an output port of a predetermined radius. The method comprises the steps of filling the channel with fluid and depositing the reservoir drop of fluid over the output of the channel. Pumping drops of the fluid are sequentially deposited at the input port of the channel to generate a pressure gradient between the fluid at the input port and the fluid at the output port whereby the fluid in the channel flows toward the output port.
Each of the pumping drops has a radius generally equal to the predetermined radius of the input port of the channel. The reservoir drop has a radius greater than the predetermined radius of the output port of the channel and has a radius greater than the radii of the pumping drops. The reservoir drop exerts a predetermined pressure on the output port of the channel. It is contemplated that the predetermined pressure exerted by the reservoir drop on the output port is generally equal to zero.